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Critical role of TLR2 and MyD88 for functional response of macrophages to a group IIA-secreted phospholipase A2 from snake venom.
- Source :
-
PloS one [PLoS One] 2014 Apr 09; Vol. 9 (4), pp. e93741. Date of Electronic Publication: 2014 Apr 09 (Print Publication: 2014). - Publication Year :
- 2014
-
Abstract
- The snake venom MT-III is a group IIA secreted phospholipase A2 (sPLA2) enzyme with functional and structural similarities with mammalian pro-inflammatory sPLA2s of the same group. Previously, we demonstrated that MT-III directly activates the innate inflammatory response of macrophages, including release of inflammatory mediators and formation of lipid droplets (LDs). However, the mechanisms coordinating these processes remain unclear. In the present study, by using TLR2-/- or MyD88-/- or C57BL/6 (WT) male mice, we report that TLR2 and MyD88 signaling have a critical role in MT-III-induced inflammatory response in macrophages. MT-III caused a marked release of PGE2, PGD2, PGJ2, IL-1β and IL-10 and increased the number of LDs in WT macrophages. In MT-III-stimulated TLR2-/- macrophages, formation of LDs and release of eicosanoids and cytokines were abrogated. In MyD88-/- macrophages, MT-III-induced release of PGE2, IL-1β and IL-10 was abrogated, but release of PGD2 and PGJ2 was maintained. In addition, COX-2 protein expression seen in MT-III-stimulated WT macrophages was abolished in both TLR2-/- and MyD88-/- cells, while perilipin 2 expression was abolished only in MyD88-/- cells. We further demonstrated a reduction of saturated, monounsaturated and polyunsaturated fatty acids and a release of the TLR2 agonists palmitic and oleic acid from MT-III-stimulated WT macrophages compared with WT control cells, thus suggesting these fatty acids as major messengers for MT-III-induced engagement of TLR2/MyD88 signaling. Collectively, our findings identify for the first time a TLR2 and MyD88-dependent mechanism that underlies group IIA sPLA2-induced inflammatory response in macrophages.
- Subjects :
- Animals
Cyclooxygenase 2 metabolism
Fatty Acids metabolism
Interleukin-10 metabolism
Interleukin-1beta metabolism
Lipid Droplets drug effects
Lipid Droplets metabolism
Macrophages drug effects
Male
Membrane Proteins metabolism
Mice, Inbred C57BL
Myeloid Differentiation Factor 88 deficiency
Perilipin-2
Prostaglandins biosynthesis
Signal Transduction drug effects
Subcellular Fractions drug effects
Subcellular Fractions metabolism
Toll-Like Receptor 2 deficiency
Up-Regulation drug effects
Group II Phospholipases A2 pharmacology
Macrophages metabolism
Myeloid Differentiation Factor 88 metabolism
Snake Venoms enzymology
Toll-Like Receptor 2 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 9
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 24718259
- Full Text :
- https://doi.org/10.1371/journal.pone.0093741